title: TP receptor-mediated release of eosinophil chemotactic activity from human bronchial smooth muscle cells.
abstract: There are reports indicating that thromboxane A(2) receptors (TP receptors) may stimulate the eosinophil accumulation in the lower airways of asthmatics, however, the mechanisms behind such an effect remain unknown. We quantified the synthesis of eosinophil chemotactic activity and eosinophilic CC chemokines, including CCL5, CCL7, CCL8, CCL11, CCL13, CCL24, and CCL26 in primary cultures of human bronchial smooth muscle cells (BSMC) stimulated with a prostanoid TP receptor agonist, IBOP (10(-9)-10(-7) M). The activation of prostanoid TP receptors in BSMC induced the release of potent eosinophil chemoattractant(s) in the presence of interleukin (IL)-4. CCL11/eotaxin-1 was the only synthesis significantly increased by IBOP co-stimulated with IL-4, and pretreatment with an anti-CCL11 antibody abrogated the eosinophil chemotactic activity released from IBOP/IL-4-stimulated BSMC. The effect of IBOP was also completely blocked by pretreatment with a prostanoid TP receptor-specific antagonist, AA-2414. IBOP had no effect on the expression of IL-4 receptor-alpha, or on the IL-4-induced phosphorylation of STAT6 in BSMC. In conclusion, activation of prostanoid TP receptors in a Th2-dominant microenvironment might exacerbate the eosinophilic inflammation of the airways by synthesis and release of CCL11 from BSMC.
authors.affiliation: Department of Medicine, Division of Pulmonary Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Koichiro
authors.initials: K
authors.lastname: Asano
authors.forename: Kyoko
authors.initials: K
authors.lastname: Niimi
authors.forename: Jun
authors.initials: J
authors.lastname: Miyata
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Shiraishi
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukunaga
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Shiomi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Oguma
authors.forename: Koichi
authors.initials: K
authors.lastname: Sayama
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Ishizaka
mesh_terms: D001249:Asthma / Q000503:physiopathology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D054413:Chemokine CCL11 / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D004804:Eosinophils / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000819:agonists / Q000378:metabolism*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D054413:Chemokine CCL11; D019742:Chemokines, CC; D005231:Fatty Acids, Unsaturated; D044244:Receptors, Thromboxane A2, Prostaglandin H2; C061750:7-(3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo(2.2.1)heptan-2-yl)-5-heptenoic acid; D015847:Interleukin-4